Cryopreserved homografts and other stentless bioprosthetic heart valves having natural tissue sewing rings

ABSTRACT

Pre-trimmed, cryopreserved homografts and other stentless bioprosthetic heart valves having natural tissue sewing rings formed thereon. The sewing ring may be formed of strip of pericardium or other suitable tissue. Material may be captured between the natural tissue sewing ring and a sub-valvular lip formed on the valve to impart a desired size or shape to the sewing ring. In the case of cryopreserved embodiments of the invention (e.g., cryopreserved human homografts) the sewing ring is attached to the valve by way of a natural tissue suture, biological glue or other attachment component that is capable of undergoing cryopreservation without breaking, excessive weakening, or other changes that prevent it from performing its attachment function.

FIELD OF THE INVENTION

The invention pertains generally to medical method/devices and moreparticularly to bioprosthetic heart valves, such as cryopreserved,pre-trimmed human homograft valves which have sewing rings formed ofnatural tissue (e.g., pericardial tissue, dura mater, tendon sheath,etc..) affixed thereto prior to cryopreservation.

BACKGROUND OF THE INVENTION

Heart valve replacement surgeries have been performed in human beingsfor many years. In these surgeries, a patient's diseased ormalfunctioning heart valve is removed and a prosthetic valve issurgically implanted in its place. The available types of prostheticheart valves include mechanical valves (i.e., valves constructed ofnon-biological materials such as titanium, carbon or steel) andbioprosthetic valves (i.e., valves formed fully or partially ofbiological tissue).

A. Bioprosthetic Heart Valves

i. Heterografts vs. Homografts

Bioprosthetic valves include heterografts (also known as xenografts) aswell as homografts (also known as allografts). Heterograft heart valvesare formed of tissue that has been harvested from a non-human animal andsubsequently implanted in a human recipient. Homograft heart valves areformed of valvular tissue that has been harvested from the heart of ahuman being and subsequently implanted in a human recipient.

Typically, heterograft heart valves are formed of tissue that has beenharvested from the heart of an animal, such as a pig, and has beentreated with a chemical fixative to preserve the tissue for subsequentimplantation.

Typically, homograft heart valves are formed of tissue that has beenharvested from cadaveric human donors, or from the explanted hearts ofhuman heart transplant recipients whose ailing hearts had healthy valvesdespite the presence of cardiomyopathy or other cardiac pathology. Theharvested homograft tissue is then treated chemically to kill anyviruses or other microbes and subsequently cryopreserved (i.e., cooledto a very low temperature by immersion in liquid nitrogen) until thetime of implantation. To date, commercially available homograft valveshave typically been provided to the surgeon in a non-trimmed state(i.e., with a substantial amount of the donor's muscle tissue (e.g.,cardiac septal muscle) affixed to the valve). Thus, prior toimplantation, the homograft must be removed from the liquid nitrogenfreezer used for the valve bank, thawed by the method recommended by themanufacturer, and then carefully trimmed of excess tissue. This trimmingprocess is laborious and not particularly standardized. Also, thistrimming process typically must be performed by a highly trainedsurgeon.

Stented vs. Unstented

Some bioprosthetic valves, known as “stented” bioprosthetic valves,incorporate a man-made stent or support frame upon which preservedallograft tissue is mounted and an annular sewing ring, formed ofman-made materials (e.g., an annular nylon core covered with a knittedpolyester sleeve), is formed about the inflow end of the valve tomaintain the inflow end of the bioprosthesis in a non-collapsed “open”configuration and to provide a firm suture-holding structure around thevalve to facilitate suturing of the valve to the annulus of therecipient. U.S. Pat. No. 4,759,758 (Gabbay) has purported to describe astented bioprosthetic heart valve formed of a man-made stent havingchemically preserved biological tissue (e.g., bovine pericardialtissue), mounted on the man-made stent to form the valve leaflets.Additionally, a quantity of preserved biological tissue or polyester(i.e., Dacron) that has been impregnated with collagen, is mounted aboutthe base of the man-made stent to form a sewing ring thereon.

Examples of commercially available stented bioprosthetic valves includethe Carpentier-Edwards®, PERIMOUNT™ Pericardial Bioprosthesis (BaxterHealthcare Corporation, Edwards CVS Division, P.O. Box 11150, Santa Ana,Calif. 92711-1150 as well as the Carpentier-Edwards® PorcineBioprosthesis (Baxter Healthcare Corporation, Edwards CVC Division, P.O.Box 11150, Santa Ana, Calif. 92711-1150). Each of these valves are ofthe heterograft type.

Others, known as “stentless” bioprosthetic valves, do not include anymanmade stent or support frame, and are formed entirely of preservedbiological tissue, and do not include any “sewing rings” formed abouttheir inflow ends.

Examples of commercially available stentless bioprosthetic valves of theheterograft type include the Edwards Prima™ Stentless Bioprosthesis(Baxter Edwards AG, Spierstrasse 5, CH-6848 Horw, Switzerland), theMedtronic Freestyle™ Aortic Root Bioprosthesis (Medtronic, Inc. 7000Central Avenue NE, Minneapolis, Minn. 55432-3576) and the St. JudeToronto™ Stentless Bioprosthesis (St. Jude Medical, Inc. One LilleheiPlaza, St Paul, Minn. 55117).

An example of a commercially available stentless bioprosthetic valves ofthe homograft type is the CryoValve™ cryopreserved aortic homograft(CryoLife Corporation, Atlanta, Ga.).

Stentless bioprosthetic valves may offer superior hemodynamicperformance when compared to their stented counterparts, due to theabsence of flow restrictions which can be created by the presence of astent and/or sewing ring. Also, the stentless bioprosthetic valves mayexhibit better post-implantation durability than the stentedbioprosthetic valves, because they provide a more flexible structurewhich serves to dissipate stress during the cardiac cycle.

Stentless valves of the homograft type are particularly advantageous inthat they exhibit excellent long-term durability and are completelydevoid of synthetic or man-made components. The absence of suchsynthetic or man-made components has been demonstrated to minimize thelikelihood of post-operative infection of homograft valves, even inpatients who suffer from active endocarditis or other infectiousprocesses within the thoracic cavity. However, the presently availablehomograft valves are associated with certain drawbacks, namely i) thatthey require a substantial amount of trimming by the surgeon prior toimplantation and ii) the absence of a defined “sewing ring” about theinflow end can cause surgeons to experience difficulty in firmly sewingthe inflow end of the homograft valve to the patient's native valeannulus.

B. Methods of Preserving Bioprosthetic Valves

Most bioprosthetic heart valves are formed at least partially of naturaltissue that contains high concentrations of connective tissue proteins.Collagen, and to a lesser extent elastin, are the major connectivetissue proteins which make-up the connective tissue matrix or frameworkof most biological tissues. The relative pliability or rigidity of eachbiological tissue is largely determined by its relative amounts ofcollagen and elastin and/or by the physical configuration (e.g.,structural lattice) and confirmation of the connective tissue matrix.

At present, the natural tissue contained in most bioprosthetic heartvalves is preserved, at the time of manufacture, by either chemicalfixation (e.g., “tanning”) or by cryopreservation (e.g., cooling to avery low temperature by imersion in liquid nitrogen). Each of thesetissue preservation techniques has certain advantages and disadvantages,as discussed more fully herebelow.

i. Chemical Fixation

The chemical fixation of biological tissues contained in bioprostheticheart valves can be accomplished by contacting the tissue with one ormore chemicals which will crosslink collagen and elastin molecules whichare present within the tissue. Such crosslinking of the collagen andelastin serves to preserve the tissue so that it may be stored until itis needed for implantation in a patient. Examples of the types ofbiological tissues that are suitable for chemical fixation includecardiac valvular tissue, blood vessels, skin, dura mater, pericardium,ligaments and tendons. These anatomical structures typically containconnective tissue matrices, formed of collagen and elastin, and thecellular parenchyma of each tissue is disposed within and supported byits connective tissue matrix.

Each collagen molecule consists of three (3) polypeptide chains whichare intertwined in a coiled helical confirmation. Chemical fixatives(i.e., tanning agents) used to preserve biological tissues generallyform chemical cross-linkages between the amino groups on the polypeptidechains within a given collagen molecules, or between adjacent collagenmolecules.

Elastin fibers are built by cross-linking (natural linkage) of repeatingunits of smaller molecules in essentially fibrous strands maintained byrigid cross-linking involving desmosine and isodesmosine. Those chemicalfixatives which are used to form cross-linkages between the amino groupsof collagen molecules also tend to form such cross-linkages betweenamino groups of elastin molecules. However, the amount of elastinpresent in most biological tissues is substantially less than the amountof collagen present therein.

When chemical cross-linkages formed between polypeptide chains within asingle collagen or elastin molecule, such cross-linking is termed“intramolecular”, while cross-linkages formed between polypeptide chainsof different collagen or elastin molecules are termed “intermolecular”.

The particular types of chemical fixative agents that have previouslybeen utilized to cross-link collagen and/or elastin in biologicaltissues include; formaldehyde, glutaraldehyde, dialdehyde starch,hexamethylene diisocyanate and certain polyepoxy compounds.

Glutaraldehyde is the most widely used agent for fixing biologicaltissues to be as bioprostheses and there are currently a number ofcommercially available glutaraldehyde-fixed bioprosthetic devices, suchas, heart valves of porcine origin having support frames or stents(Carpentier-Edwards® Stented Porcine Bioprosthesis; Baxter HealthcareCorporation; Edwards CVS Division, Irvine, Calif. 92714-5686),prosthetic heart valves formed of a metal frame having leaflets formedof bovine pericardial tissue mounted on said frame (e.g.,Carpentier-Edwards®Pericardial Bioprosthesis, Baxter HealthcareCorporation, Edwards CVS Division; Irvine, Calif. 92714-5686) andstentless porcine aortic prostheses (e.g., Edwards® PRIMA™ StentlessAortic Bioprosthesis, Baxter Edwards AG, Spierstrasse 5, GH6048, Horn,Switzerland).

One problem associated with the implantation of bioprosthetic heartvalves that have been preserved by chemical fixation is that they tendto undergo in situ calcification following implantation followingimplantation. Such calcification can result in undesirable stiffening,degradation and premature failure of the bioprosthesis. Both intrinsicand extrinsic calcification have been known to occur, although the exactmechanism(s) by which such calcification occurs is unknown.

The factors which determine the rate at which chemically-fixedbioprosthetic grafts undergo calcification have not been fullyelucidated. However, factors which are thought to influence the rate ofcalcification include:

a) patient's age;

b) existing metabolic disorders (i.e., hypercalcemia, diabetes, etc.);

c) dietary factors;

d) race;

e) infection;

f) parenteral calcium administration;

g) dehydration;

h) distortion/mechanical factors;

i) inadequate coagulation therapy during initial period followingsurgical implantation; and

j) host tissue responses.

Glutaraldehyde-fixed bioprosthetic grafts have been observed to calcifysooner than grafts which have been fixed by non-aldehyde fixativeagents. Thus, non-aldehyde fixatives, such as polyepoxy compounds (e.g.,Denacol Ex-810, Denacol Ex-313) may be useful for manufacturingbioprosthetic graft materials which exhibit improved (i.e., lessened)propensity for calcification.

Other techniques for mitigation calcification of implanted biologicaltissues are described in U.S. Pat. No. 4,885,005 (Nashef et al.)entitled Surfactant Treatment of Implantable Biological Tissue ToInhibit Calcification; U.S. Pat. No. 4,648,881 (Carpentier et al.)entitled, “Implantable Biological Tissue and Process For PreparationThereof”; U.S. Pat. No. 4,976,733 (Girardot) entitled, “Prevention ofProsthesis Calcification”; U.S. Pat. No. 4,120,649 (Schechter) entitled,“Transplants”; U.S. Pat. No. 5,002,2566 (Carpentier) entitled,“Calcification Mitigation of Bioprosthetic Implants”; EP 103947A2(Pollock et al.) entitled, “Method For Inhibiting Mineralization ofNatural Tissue During Implantation” and WO84/01879 (Nashef et al.)entitled, “Surfactant Treatment of Implantable Biological Tissue toInhibit Calcification”; and, in Yi, D., Liu, W., Yang, J., Wang, B.,Dong, G., and Tan, H.; Study of Calcification Mechanism andAnti-calcification On Cardiac Bioprostheses Pgs. 17-22, Proceedings ofChinese Tissue Valve Conference, Beijing, China, June 1995.

The overall biocompatability (e.g., antigenicity and immunogenicity) ofthe fixed graft material can significantly affect the severity ofpost-implantation graft calcification, and may also be a factor in theoccurrence of other undesirable sequelae such as platelet activation,thrombogenesis, local inflammation, and/or graft failure.

iii. Cryopreservation

Cryopreservation is a tissue preservation technique wherein the tissueis cooled to an extremely low temperature and maintained in a frozenstate. This cryopreservation of the tissue is typically accomplished byplacing the tissue in a bath solution containing certain cryoprotectants(i.e., chemicals that protect the tissue from damage or degradationduring freezing) and immersing it in liquid nitrogen to effect rapid andextreme cooling of the tissue and bath solution. The tissue then remainsin the liquid nitrogen until it is desired to implant the tissue. Atthat time, the tissue is removed from the liquid nitrogen and thawed.Examples of specific cryopreservation techniques that have heretoforebeen used with homograft heart valves are described in U.S. Pat. No.4,890,457 (McNally, et al) and U.S. Pat. No. 5,632,778 (Goldstein), theentire disclosures of which are expressly hereby incorporated byreference.

SUMMARY OF THE INVENTION

The present invention overcomes shortcomings of prior cryopreservedhomograft heart valves by providing a pre-trimmed, specifically sized,cryopreserved homograft that has a sewing ring formed of cryopreservablenatural tissue (e.g, pericardium) affixed at least partially about theinflow end of the homograft. Marking(s) may be formed on the naturaltissue sewing ring to indicate a location(s) through which sutures maybe passed to ensure that such sutures will engage (i.e., pass through)underlying annular connective tissue of the homograft.

Additionally, the present invention overcomes certain shortcomings ofchemically fixed stentless heart valve bioprostheses of the prior art byproviding a stentless bioprosthesis that has a sewing ring formed ofnatural tissue (e.g., pericardium) formed at least partially about theinflow end of the bioprosthesis. Such natural tissue sewing ring is lesslikely to become infected that other types of sewing rings made fully orpartially of man-made materials such as polyester mesh.

Further aspects and objects of the present invention will becomeapparent to those of skill in the relevant art upon reading andunderstanding of the following detailed description of certain preferredembodiments and examples, and the drawings to which it refers.

BRIEF DESCRIPTION OF THE DRAWINGS

FIGS. 1a-1 c are step-by-step showings of a preferred method formounting a natural tissue sewing ring about the inflow end of an aortichomograft.

FIG. 2a is a perspective view of an aortic homograft of the presentinvention having a natural tissue sewing ring that extends 270 degreesabout the inflow end of the bioprosthesis.

FIG. 2b is a perspective view of another aoritc homograft of the presentinvention having a natural tissue sewing ring that extends 360 degreesabout the inflow end of the bioprosthesis.

FIGS. 3a and 3 b are showings of a preferred method of passing suturesthrough the natural tissue sewing ring of an aortic homograft to attachthe inflow end of the homograft to the native aortic annulus of therecipient patient.

DETAILED DESCRIPTION OF PREFERRED EMBODIMENT

The following detailed description, and the figures to which it refers,are provided for the purpose of describing example(s) and specificembodiment(s) of the invention only and are not intended to exhaustivelydescribe all possible examples and embodiments of the invention.

A. Harvesting, Assembly and Preparation of an Aortic Homograft of thePresent Invention

FIGS. 1a-1 c show, in step-by-step fashion, a preferred method forconstructing an aortic homograft 10 of the present invention.

ii. Harvesting and Pre-Trimming of Aortic Segment

As shown, a segment of ascending aorta 20 having remnants of the rightand left coronary arteries 18R, 18L extending therefrom and the leaflets22 of the donor's aortic valve positioned therewithin is excised andharvested from the heart of a human donor. Typically, a quantity ofmuscle 16 and fiberous connective tissue of one mitral valve leaflet 17will remain attached to the inflow end IE of the harvested aorticsegment 20. Such muscle 16 and fiberous connective tissue 17 issubsequently trimmed to form a subvalvular tissue lip 23 that extendsabout the inflow end IE, beneath the valve leaflets 22. As indicated inFIG. 1c, the upper portion of this subvalvular tissue lip 23 _((upper))is formed of annular connective tissue and the lower portion of thissubvalvular lip 23 _((lower)) is formed of muscle tissue. Thissubvalvular tissue lip 23 is typically 3-4 mm in length.

ii. Harvesting of Sewing Ring Tissue Strip

A generally rectangular tissue strip 14 is harvested from a donor andsuch tissue strip 14 is then used to form the natural tissue sewing ring14A. The tissue strip 14 preferably comprises pericardial tissue thathas been harvested from the same donor as the aortic segment 20.However, it will be appreciated that other types of relatively durabletissue may also be useable to form the sewing ring 14A. Examples ofother types of tissue that may be used include dura mater, plantarfascia or the sheaths of tendons. It will be further appreciated thatthe tissue strip 14 could be harvested from a human donor other than thedonor from whom the aortic segment was harvested (e.g., from therecipient into whom the homograft is to be implanted or another humandonor) or from another animal species (e.g., porcine, bovine, etc.). Thetissue strip 14 is trimmed to a size that is suitable to fit upon theinflow end IE of the aortic segment 20 as shown in FIG. 1c.

iii. Attaching the Sewing Ring Tissue Strip to the Aortic Segment

As shown in FIG. 1c, the tissue strip 14 is curled over or wrappedpartially around the subvalvular tissue lip 23 in a generally unshapedconfiguration, and suture material 27 is passed through both sides ofthe tissue strip 14 at or slightly above the junction of the upper andlower portions 23 _((upper)), 23 _((lower)) of the lip 23, to form acontinuous suture line 27A. This suture line 27A secures the tissuestrip 14 to the inflow end IE if the aortic segment 20, thus forming thenatural tissue sewing ring 14A. The suture line 27A may be formed of acolored or readily visible suture material to clearly delineate theboundary between the upper and lower portions 23 _((upper)), 23_((lower)) of the tissue lip 23, such that subsequent placement ofsutures above this suture line 27 a will ensure that those subsequentsutures will pass through the relatively strong annular connectivetissue of the tissue lip's upper portion 23 _((upper)) rather thanthrough the muscle tissue of the tissue lip's lower portion 23_((lower)). Optionally, a second suture line (not shown) may be placedabove suture line 27A in substantial parallel therewith, but below thevalve leaflets 22. Such second suture line (not shown) will thus denotea zone (i.e., a region between the lower suture line 27A and the secondsuture line formed thereabove but not shown on the drawings) throughwhich subsequent sutures may be passed with assurance that thosesubsequent sutures will a) pass through the relatively strong annularconnective tissue of the tissue lip's upper portion 23 _((upper)) ratherthan through the muscle tissue of the tissue lip's lower portion 23_((lower)) and b) not injure or impair the valve leaflets 22.

In some cases, the tissue strip 14 will be attached such that it extendsapproximately 270 degrees around the inflow end IE of the aortic segment20 while, in other cases, the tissue strip 14 will be attached such thatit extends fully 360 degrees around the inflow end IE of the aorticsegment 20.

In some cases a quantity of additional material or fabric (not shown)such as additional layers of sewing ring tissue strip 14, a mass ofbiological matter such as a biological glue, fibrin glue, collagenousmaterial, gelatinous material, polyester mesh, nylon, felt, or othermaterial may be positioned and captured between the tissue lip 23 andthe tissue strip 14. This may serve to impart additional bulk or aspecific shape (e.g., an oval, oblong or crescent shape) to the sewingring 14A. The desirability of imparting a slightly oblong, oval orcrescent shape to the sewing ring 14A is explained in more detailherebelow in connection with the surgical implantation of the homograft10.

It will be appreciated that, where the homograft is to be cryopreserved,the sewing ring tissue strip 14, any additional tissue or bulkingmaterial, and the suture material 27 used to attach the sewing ringtissue strip 14 to the tissue lip 23 must be formed of material that iscapable of being frozen at extremely low cryopreservation temperatureswithout degrading, crumbling, breaking or otherwise losing the abilityto firmly affix the sewing ring 14A in its desired position on thehomograft 10. For this reason, it is desirable that the suture material27 be of a cryopreservable natural (or synthetic) material (e.g., catgut or metal wire) or a “suture” crafted from a narrow strip ofrelatively strong donor tissue such as dura mater, pericardium orfascia. In this regard, as an alternative to or in addition to, thesuture line 27A a cryopreservable adhesive material may be used to affixthe sewing ring 14A to the tissue lip 23 of the aortic segment 20. Forexample, a biological adhesive such as a fibrin glue may withstand theextremely low temperature of cryopreservation and would thus besufficiently cryopreservable and suitable for this purpose.

The fabrication of this sewing ring 14A on the inflow end IE of theaortic segment 20 completes the initial fabrication of the aortichomograft 10.

iv. Bioburden Reduction or Sterilization

Prior to, during and/or after the initial fabrication of the homograft10 has been completed, the homograft 10 and/or the components thereofmay be immersed one or more times in a suitable microbicidal orantibiotic solution to reduce any microbial or bacterial content of thetissue. Alternatively or additionally, the homograft 10 may besterilized by any sterilization technique that is suitable for suchhomograft tissue.

V. Cryopreservation

After the homograft 10 has been sterilized, it is subjected to asuitable cryopreservation process, examples of which are described inU.S. Pat. No. 4,890,437 (McNally, et al) and U.S. Pat. No. 5,632,778(Goldstein), the entire disclosures of which are expressly herebyincorporated by reference. At the time of cryopreservation, thehomograft 10 may be placed in a sealed in a pouch or container that hasbeen filled with a storage solution containing certain cryoprotectants(e.g., substances which when added during the freezing of tissue orcells help to prevent freezing damage).

Although cryopreservation is believed to be the preferred method forpreservation of homografts 10 of this type, it will be appreciated thatother tissue preservation techniques, such as the chemical fixation or“tanning” techniques described hereabove, may be used to preserve theentire homograft 10 or portions thereof such as the sewing ring tissuestrip 14.

B. Surgical Replacement of a Malfunctioning Aortic Valve Using an AorticHomograft of the Present Invention

FIGS. 3a and 3 b illustrate one aspect of the preferred methods forsurgical implantation of a pre-trimmed, cryopreserved, sewingring-equipped aortic homograft 10 of the present invention. Detaileddescriptions of alternative procedures for implanting this homograft 10are set forth herebelow. The procedural descriptions serve to illustratecertain advantages of this pre-trimmed, sewing-ring equipped homograft10 of the present invention over the prior art aortic homografts.

Initially, the pre-trimmed, sewing-ring equipped aortic homograft 10 isthawed and removed from its protective pouch. In contrast to aortichomografts of the prior art, no trimming of this homograft 10 isrequired after thawing, as excess septal muscle tissue has previouslybeen trimmed away prior to attachment of the natural tissue sewing ringand prior to cryopreservation.

The patient is anesthetized and an incision is made in the chest to gainaccess to the patient's heart. In most cases, either a) a midlinesternotomy incision or b) a minimal approach using a lower ½ sternotomyincision, is used. The patient is then placed on cardiopulmonary bypassusing a single venous cannula (two stage) with oxygenated blood returnprovided to the ascending aorta. In cases where substantial infection ofthe aortic root is present, two venous cannulae may be used to allow forentry through the right atrium or ventricle if such entry should bedeemed necessary during the procedure. A vent catheter is insertedthrough the right superior pulmonary vein and into the left atrium andleft ventricle.

The ascending aorta is then occluded at the pericardial reflection and aflow of hypothermic cardioplegia solution is administered to the heartto assure total electro mechanical arrest and to protect the myocardiumfrom ischemic injury during the procedure. The cardioplegia solution ispreferably retro-perfused through the coronary veins, by way of acatheter that has been inserted into the coronary sinus. This type ofretrograde venous perfusion is preferred over antegrade arterialperfusion because it can be fully effective even in patients who sufferfrom severe aortic valve incompetence and, additionally, because itavoids the need for placing any perfusion cannula in the aortic root.

Thereafter, the endogenous aortic valve is removed and the homograft 10is implanted in its place, by one of several possible techniques,including a) complete aortic root replacement techniques wherein theentire aortic root including the aorto-coronary junctions are replacedby the homograft 10 and b) sub-coronary techniques wherein only theportion of the homograft proximal to the coronary ostia is implanted(leaving the recipient patient's existing aorto-coronary anatomy intact). Examples of a complete aortic root replacement technique and asubcoronary technique are described in significant detail herebelow,with reference to the showings of FIGS. 2a-3 b. It is to be appreciated,however, that these descriptions are merely examples of possibleimplantation techniques and numerous other techniques or modificationsthereof may also be used.

i. Complete Aortic Root Homograft Technique

In the complete aortic root technique, the ascending aorta is dividedabove the sinotubular junction. The sinus aorta surrounding the coronaryarteries is retained such that “buttons” of tissue surround the free endof each of the left and right main coronary arteries. The remainder ofthe sinus aorta is excised leaving only fibrous aortic valve attachmentswhich are normal and uninvolved with the disease process which is beingtreated.

The diameter of the aortic root at the level of valve cusp attachment(annulus) is determined using standard sizing devices. An appropriatelysized aortic homograft 10 of the present invention is selected forimplantation. Sizing of the homograft 10 to be used in this completeaortic root replacement is of less importance than in a freehand valvereplacement because the homograft 10 will not be enclosed by host aorta.Nonetheless, it is desirable for the internal diameter of the selectedhomograft may be slightly (e.g., 1-2 mm) smaller than the measureddiameter of the aortic annulus. Such down-sizing of the aortic homograftcan allow for minor post-operative shrinkage of the graft cusp tissuesand for absorption of the septal myocardium. However, too muchdownsizing of the aortic homograft can result in aortic valveincompetence 3 or 4 months after operation. The presence of the naturaltissue sewing ring 14A formed about the inflow end IE of the homograft10 facilitates firm suturing of the slightly undersized homograft 10 tothe annular connective tissue ACT surrounding the homograft 10 withouttearing through of the sutures as can occur with the homografts of theprior art that do not include such sewing ring 14A. Thus, the presenceof the sewing ring 14A serves to facilitate such purposeful undersizingof the cusp of the homograft 10.

A proximal suture line attaching the homograft 10 to the leftventricular outflow tract is begun by placing simple interrupted ormattress stitches 34 of appropriate suture material (e.g., 4/0 Ethibondbraided suture material) through the annular connective tissue ACTsurrounding the patient's valve annulus AN, as shown in FIG. 3A. Incases where the annular connective tissue ACT has been removed ordestroyed by the disease process, these stitches 34 may be placedthrough septal myocardium and the unsupported anterior leaflet of themitral valve and/or roof of left atrium to gain sufficientsuture-holding capacity in the absence of sufficient annular connectivetissue ACT.

After the sutures 34 have been passed through the patient's annularconnective tissue ACT, they are similarly passed through the naturaltissue sewing ring 14A at a location whereby they pass through theannular connective tissue of the upper portion of the homograft'ssubvalvular tissue lip 23 _((upper)) located between the opposite sidesof the pericardial tissue strip 14. In instances where the suture line27A has been located at or slightly above the junction of the upper andlower tissue lip portions 23 _((upper)), 23 _((lower)) such suture line27A may be used as a guide and the surgeon may place these sutures 34just above that suture line 27A thereby ensuring that these sutures 34will pass through the relatively strong connective tissue of thehomograft's upper tissue lip 23 _((upper)). Where a second, parallelsuture line (not shown) has also been provided, as described hereabove,the surgeon may place these sutures 34 above the lower suture line 27Abut below the upper parallel suture line (not shown), thereby ensuringthat the sutures 34 so placed will pass a) through the relatively strongconnective tissue of the homograft's upper tissue lip 23 _((upper)) butb) below the valve leaflets 22 so as not to interfere with, injure orimpair the valve leaflets.

In the past, some surgeons have elected to place a reinforcing collar,formed of a strip of polytetrafluoroethylene (i.e., Teflon) feltmaterial or a cut segment of the recipient's pericardium approximately 5mm wide, between the inflow end of a homograft (without a sewing ring)and the surrounding tissue of the recipient's annulus AN to ensure ahemostatic proximal suture line and to prevent excessive dilation of theroot of the aortic homograft 10.

The homograft is then downwardly slipped over the sutures 34 until thenatural tissue sewing ring 14A of the homograft 10 is in firm abuttmentwith the annular connective tissue ACT (or other tissue) surrounding thehost annulus AN. The sutures 34 are then tied down. The strength andtear resistance of the natural tissue sewing ring 14A allows the surgeonto firmly tie these sutures 34 to effectively prevent leakage at theproximal suture line formed thereby.

The coronary ostia of the graft are enlarged to create openings 36R and36L that are sized to receive the “buttons” of tissue formed on the endsof the host coronary arteries. These coronary buttons are thenanastomosed to the homograft tissue surrounding these openings 36R, 36Lusing continuous stitches of 4/0 or 5/0 polypropylene suture.

The repair is completed by end-to-end anastomosis of the outflow end OEof the homograft 10 to the patient aorta. Continuous stitches of 4/0polypropylene are used to form this distal anastomosis.

ii. Subcoronary Aortic Homograft Technique

In this subcoronary technique, only the portion of the homograftproximal to the coronary ostia is implanted. The remaining distalportion of the homograft's aortic segment 14, including the coronaryartery remnants 18R, 18L, are cut away and discarded.

The ascending aorta is divided above the sinotubular junction. Thisprovides optimal exposure while retaining the natural relationships ofthe aortic root. The aortic valve is excised and the annular connectivetissue ACT surrounding the annulus AN and sinus aorta are debrided ofany calcium deposits. The diameter of the aortic root at the level ofvalve cusp attachment (annulus) is determined using a sizing device ofthe type well known in the art and an appropriately sized homograft 10of the present invention is selected by the surgeon as describedhereabove with respect to the full root procedure.

The sinus aorta is trimmed away from the valve cusps leaving a 3-4 mmrim of aorta beyond the attachment of the cusps. Most of the sinus aortawill be removed from the right and left coronary sinuses. Thenoncoronary sinus aorta remains intact in order to fix the position ofthe two adjacent commissures. The aorta is shortened to approximatelythe same distance above the top of the commissural attachment betweenthe left and right sinuses.

Three stitches may be used to attach the homograft 10 to the outflowtract. For example, the first stitch may be of an appropriate material(e.g., 3/0 polypropylene) with two small strong needles (RB-1). Amonofilament suture of this type may be chosen due to its needlestrength and because the suture loops slide easily without tendency tocut through the homograft 10 tissue. This suture is passed through thegraft septal muscle below the appropriate commissure and then throughthe host aortic outflow tract below the medial commissure between theright and left coronary sinuses. This first stitch is placed below theannulus of the host aortic valve. Thereafter, two alignment sutures areplaced to ensure alignment of the homograft to the aortic root. Thesealignment stitches are formed of appropriate suture material (e.g., 4/0polypropylene) and are subsequently removed as the primary suture linecomes to involve their position. These stitches are placed beneath theappropriate commissure of the graft, directly below the anterior andposterior commissures of the host aorta.

The homograft 10 is then advanced into position on the aortic root whilebeing guided by the alignment sutures. The commissures of the graft areinverted through its annulus AN into the left ventricle of the host,thereby exposing the natural tissue sewing ring 14A on the inflow end IEof the homograft 10. A knot is placed in the primary suture and the staysutures are pulled taught to bring the homograft into alignment with theaortic outflow tract.

A proximal anastomosis is formed by passing sutures 34 are passedthrough the natural tissue sewing ring 14A and the annular connectivetissue ACT. The patient's aortic annulus AN is usually not truly annularbut rather somewhat oblong or crescent shaped. Thus, the stitches 34 mayactually be placed below the fibrous “annulus” AN and in thesub-commissural region or interleaflet triangle and will come throughthis fibrous tissue at the mid-point of the aortic sinus. Alternatively,it will be appreciated that the natural tissue sewing ring 14A may bebuilt-up in selected regions by the presence of additional layers ofsewing ring tissue (e.g., pericardium) or an other cryopreservablebulking material (e.g., biological glue, fibrin glue, other tissue, etc)to cause the sewing ring to have an oblong, oval or somewhat crescentshape so as to more precisely match with the native annulus AN.

The commissures of the aortic homograft 10 are then pulled out of theleft ventricle so that the valve leaflets 22 assume a normal positionand configuration. The sinus aorta of the homograft 10 is theanastomosed to the host aorta by continuous suture using an appropriatesuture material such as 4/0 polypropylene. Separate stitches are usedfor the right and left aortic sinuses, and such stitches are positionedbelow the coronary ostia, in the sinus of Valsalva. As the suturingproceeds up the commissure, the stitches in the host aorta arepreferably placed away from the actual fibrous commissure in the tissueof the aortic sinus so as to cause homograft commissure to be flatagainst the host aortic wall. The final stitches securely fasten thecommissure of the homograft 10 to the aortic wall.

The placement of these distal sutures continues in each aortic sinusuntil the homograft 10 has been completely attached. Generally, theright coronary sinus is completed first, sewing from the center point ofthe sinus to each of the commissures using opposite ends of the suture.The left sinus is then sewn in a similar manner. The noncoronary sinusaorta of the aortic segment 14 of the homograft 10 is trimmed so as tobe flush with the cut edge of the aorta so that the two edges may beapproximated and joined simply by over and over continuous suturing.

The repair is then completed by anastomosis of the ascending aorta tothe aortic root, the patient is removed from cardiopulmonary bypass, andthe thoracotomy (sternotomy) incision is closed.

It will be appreciated that the invention has been described hereabovewith reference to certain examples or preferred embodiments as shown inthe drawings. Various additions, deletions, changes and alterations maybe made to the above-described embodiments and examples withoutdeparting from the intended spirit and scope of this invention. Forexample, the homograft need not be formed of aortic tissue but, rather,may be formed on the donor's pulmonary valve and adjacent segment ofpulmonary artery (i.e., a pulmonary homograft). Also, the sewing ringtissue strip 14 used to form the natural tissue sewing ring 14A need notnecessarily be made of cryopreserved tissue harvested from the samedonor as the valve itself, but rather may be a chemically fixed(“tanned”) instead of cryopreserved and/or may have been harvested fromany suitable human or animal (e.g., porcine, bovine) donor.Additionally, this invention includes cryopreserved stented or stentlessheterografts formed wholly or partially of tissues that have beenharvested from non-human animal species (e.g., porcine, bovine), such aspigs that have been genetically altered or genetically engineered toproduce tissue that is human-compatable and can be transplanted intohuman recipients without rejection or significant immunogenic reaction.Accordingly, it is intended that all such additions, deletions, changesand alterations be included within the scope of the following claims.

What is claimed is:
 1. A cryopreserved heart valve homograft comprising: a generally tubular segment of vascular tissue harvested from a mammalian donor, said tubular segment having an inflow end and an outflow end and a plurality of valve leaflets disposed within said tubular segment a spaced distance above the inflow end, the inflow end of said tubular segment being trimmed to form a subvalvular lip; and, a sewing ring formed of tissue harvested from a human donor, said sewing ring being attached by a cryopreservable attachment component to said subvalvular lip; said tubular segment having said sewing ring attached thereto being cryopreserved.
 2. A homograft according to claim 1 wherein the sewing ring comprises pericardium.
 3. A homograft according to claim 1 wherein said generally tubular segment comprises a segment of the donor's aorta and said leaflets comprise the donors aortic valve leaflets.
 4. A homograft according to claim 1 wherein said generally tubular segment comprises a segment of the donors pulmonary artery and said leaflets comprise the donor's pulmonary valve leaflets.
 5. A homograft according to claim 1 wherein the cryopreservable attachment component is selected from the group consisting of: a cryopreservable suture material; catgut suture material; suture material prepared from natural tissue; a cryopreservable adhesive; a biological adhesive; a fibrin glue; possible combinations thereof.
 6. A homograft according to claim 1 wherein the sewing ring comprises a tissue that is selected from the group of tissues consisting of: pericardium; dura mater; tendon sheath; fascia; and, possible combinations thereof.
 7. A homograft according to claim 1 wherein the sewing ring further comprises cryopreservable material that is captured between the subvalvular lip and said sewing ring tissue.
 8. A homograft according to claim 7 wherein the cryopreservable material captured between the subvalvular lip and said sewing ring tissue is located to impart a desired shape to said sewing ring.
 9. A homograft according to claim 1 wherein the subvalvular lip has an upper portion formed substantially of connective tissue and a lower portion formed substantially of other than connective tissue, and wherein the homograft further comprises marking formed on the sewing ring to denote the location of said upper portion of the subvalvular lip.
 10. A homograft according to claim 1 wherein the subvalvular lip has been trimmed to provide a sewing ring of predetermined length and diameter.
 11. A cryopreserved stentless heart valve bioprosthesis comprising: a generally tubular segment of vascular tissue that has an inflow end and an outflow end; a plurality of valve leaflets disposed within said tubular segment a spaced distance above the inflow end such that a subvalvular lip exists at the inflow end of the tubular segment beneath the valve leaflets; a sewing ring that has been attached to and extends at least partially about the subvalvular lip of said tubular segment, said sewing ring comprising sewing ring tissue that has been harvested from a mammalian donor; and a cryopreservable attachment component attaching the sewing ring to said subvalvular lip.
 12. A stentless heart valve bioprosthesis according to claim 11 wherein the sewing ring comprises a strip of pericardium that has been attached to the subvalvular lip of the generally tubular segment.
 13. A stentless aortic valve bioprosthesis according to claim 11 wherein said generally tubular segment comprises a segment of the donor's aorta and said leaflets comprise the donor's aortic valve leaflets.
 14. A stentless pulmonary valve bioprosthesis according to claim 11 wherein said generally tubular segment comprises a segment of the donor's pulmonary artery and said leaflets comprise the donors pulmonary valve leaflets.
 15. A stentless heart valve bioprosthesis according to claim 11 wherein at least the tubular segment and the leaflets were harvested from a donor of the same species as the recipient into whom the stentless heart valve homograft is to be implanted.
 16. A stentless heart valve bioprosthesis according to claim 11 wherein the sewing ring comprises tissue that was harvested from a donor of the same species as the recipient into whom the stentless heart valve homograft is to be implanted.
 17. A stentless heart valve bioprosthesis according to claim 11 wherein the sewing ring comprises a tissue that is selected from the group of tissues consisting of: pericardium; dura mater; tendon sheath; fascia; and, possible combinations thereof.
 18. A stentless heart valve bioprosthesis according to claim 11 formed entirely of biological tissue that is cryopreservable.
 19. A stentless heart valve bioprosthesis according to claim 18 wherein the cryopreservable attachment component is selected from the group consisting of: a cryopreservable suture material; suture material prepared from natural tissue; a cryopreservable adhesive; a biological adhesive; a fibrin glue; possible combinations thereof.
 20. A stentless heart valve bioprosthesis according to claim 11 wherein the biological tissue thereof is preserved by chemical fixation.
 21. A stentless heart valve bioprosthesis according to claim 11 wherein the sewing ring further comprises a quantity of material that is captured between the subvalvular lip and said sewing ring tissue.
 22. A stentless heart valve bioprosthesis according to claim 21 wherein the material captured between the subvalvular lip and said sewing ring tissue is sized and located to impart a desired shape to said sewing ring.
 23. A stentless heart valve prosthesis according to claim 11 formed entirely of cryopreservable material.
 24. A stentless heart valve prosthesis according to claim 23 which has been cryopreserved.
 25. A stentless heart valve prosthesis according to claim 24 wherein the bioprosthesis is a heterograft formed of tissue harvested from a non-human species.
 26. A stentless heart valve prosthesis according to claim 25 wherein the animal from which the tissue is harvested was genetically engineered to produce tissue suitable for transplantation into a human recipient without substantial immunogenic rejection.
 27. A cryopreserved heart valve homograft comprising: a generally tubular segment of vascular tissue harvested from a mammalian donor, said tubular segment having an inflow end and an outflow end and a plurality of valve leaflets disposed within said tubular segment a spaced distance above the inflow end, the inflow end of said tubular segment being trimmed to form a subvalvular lip; a sewing ring formed of tissue harvested from a human donor; and a cryopreservable attachment component attaching the sewing ring to said subvalvular lip, said cryopreservable attachment component been selected from the group consisting of: a cryopreservable suture material; and a cryopreservable adhesive, said tubular segment having said sewing ring attached thereto using said cryopreservable attachment component been cryopreserved.
 28. A homograft according to claim 27 wherein the sewing ring comprises pericardium.
 29. A homograft according to claim 27 wherein the sewing ring comprises a tissue that is selected from the group of tissues consisting of: dura mater; tendon sheath; fascia; and, possible combinations thereof.
 30. A homograft according to claim 27 wherein said generally tubular segment comprises a segment of the donor's aorta and said leaflets comprise the donor's aortic valve leaflets.
 31. A homograft according to claim 27 wherein said generally tubular segment comprises a segment of the donor's pulmonary artery and said leaflets comprise the donor's pulmonary valve leaflets.
 32. A homograft according to claim 27 wherein the sewing ring further comprises cryopreservable material that is captured between the subvalvular lip and said sewing ring tissue.
 33. A homograft according to claim 32 wherein the cryopreservable material captured between the subvalvular lip and said sewing ring tissue is located to impart a desired shape to said sewing ring.
 34. A homograft according to claim 27 wherein the subvalvular lip has an upper portion formed substantially of connective tissue and a lower portion formed substantially of other than connective tissue, and wherein the homograft further comprises marking formed on the sewing ring to denote the location of said upper portion of the subvalvular lip.
 35. A homograft according to claim 27 wherein the subvalvular lip has been trimmed to provide a sewing ring of predetermined length and diameter.
 36. A stentless heart valve bioprosthesis comprising: a generally tubular segment of vascular tissue that has an inflow end and an outflow end; a plurality of valve leaflets disposed within said tubular segment a spaced distance above the inflow end such that a subvalvular lip exists at the inflow end of the tubular segment beneath the valve leaflets; a sewing ring that has been attached to and extends at least partially about the subvalvular lip of said tubular segment, said sewing ring comprising sewing ring tissue that has been harvested from a mammalian donor; and, a cryopreservable attachment component attaching the sewing ring to said subvalvular lip selected from the group consisting of: a cryopreservable suture material; and a cryopreservable adhesive.
 37. A stentless heart valve bioprosthesis according to claim 36 wherein the sewing ring comprises a strip of pericardium that has been attached to the subvalvular lip of the generally tubular segment.
 38. A stentless heart valve bioprosthesis according to claim 36 wherein the sewing ring comprises a tissue that is selected from the group of tissues consisting of: dura mater; tendon sheath; fascia; and, possible combinations thereof.
 39. A stentless aortic valve bioprosthesis according to claim 36 wherein said generally tubular segment comprises a segment of the donor's aorta and said leaflets comprise the donor's aortic valve leaflets.
 40. A stentless pulmonary valve bioprosthesis according to claim 36 wherein said generally tubular segment comprises a segment of the donor's pulmonary artery and said leaflets comprise the donor's pulmonary valve leaflets.
 41. A stentless heart valve bioprosthesis according to claim 36 wherein at least the tubular segment and the leaflets were harvested from a donor of the same species as the recipient into whom the stentless heart valve homograft is to be implanted.
 42. A stentless heart valve bioprosthesis according to claim 36 wherein the sewing ring comprises tissue that was harvested from a donor of the same species as the recipient into whom the stentless heart valve homograft is to be implanted.
 43. A stentless heart valve bioprosthesis according to claim 36 formed entirely of biological tissue that is cryopreservable.
 44. A stentless heart valve bioprosthesis according to claim 36 wherein the biological tissue thereof is preserved by chemical fixation.
 45. A stentless heart valve bioprosthesis according to claim 36 wherein the sewing ring further comprises a quantity of material that is captured between the subvalvular lip and said sewing ring tissue.
 46. A stentless heart valve bioprosthesis according to claim 45 wherein the material captured between the subvalvular lip and said sewing ring tissue is sized and located to impart a desired shape to said sewing ring.
 47. A stentless heart valve prosthesis according to claim 36 formed entirely of cryopreservable material.
 48. A stentless heart valve prosthesis according to claim 47 which has been cryopreserved.
 49. A stentless heart valve prosthesis according to claim 48 wherein the bioprosthesis is a heterograft formed of tissue harvested from a non-human species.
 50. A stentless heart valve prosthesis according to claim 49 wherein the animal from which the tissue is harvested was genetically engineered to produce tissue suitable for transplantation into a human recipient without substantial immunogenic rejection. 